OVERVIEW: What every practitioner needs to know

Are you sure your patient has glaucoma? What are the typical findings for this disease?

In primary infantile glaucoma, the classic triad of blepharospasm, photophobia, and epiphora (tearing) is recognized at birth or in the first few years of life. These findings are often bilateral and asymmetric. Bilateral cases of primary infantile glaucoma tend to have a later presentation due to the lack of recognition by the parents and physician. Cases that present at birth are generally more severe and harder to treat. Secondary infantile glaucoma may present with the same triad, but with another anomaly affecting the drainage system of the eye such as Sturge-Weber, aniridia, retinoblastoma, uveitis, or retinopathy of prematurity. Aphakic glaucoma is very common after cataract extraction in the pediatric population.

Juvenile glaucoma occurs from late childhood into early adulthood and is diagnosed after the first decade of life, and is thought to have the same pathophysiology as primary infantile glaucoma.

What are other common findings on physical examination?

In addition to the classic triad described above, many patients with primary infantile glaucoma may also have increased intraocular pressure (IOP), megalocornea, corneal edema, buphthalmos (enlargement of the globe) (See Figure 1), conjunctival injection, and strabismus. Increasing myopia, ansiometropia, amblyopia, and increased optic nerve cupping may also be diagnosed by the pediatric ophthalmologist and support the diagnosis of glaucoma.

Figure 1.

Buphthalmos of the right eye in a child due to primary congenital glaucoma Photo courtesy of Robert W. Enzenauer, MD

Increased Corneal Diameter:

Normal corneal diameter in an infant is between 9.5 and 10.5mm horizontally and can increase to 11 mm at the age of 1 year. A child’s cornea will reach its adult size of 12mm at age 2 or 3 years. An infant with a horizontal corneal diameter of 12mm should be promptly evaluated for glaucoma. Corneal diameter is measured most accurately using calipers on the anesthetized eye. This is often done at the bedside and then confirmed during an examination under anesthesia.

Cloudy Cornea:

Glaucoma can cause clouding of the cornea from edema and can range from virtually undetectable to a completely white cornea. Corneal edema occurs because the increased intraocular pressure causes dysfunction of the innermost layer of corneal cells, the endothelium, whose job is to dehydrate the cornea and keep it clear. Additionally, increased intraocular pressure may cause breaks in the second most posterior layer of the cornea, Descemet’s membrane. This results in horizontal or oblique lines in the posterior cornea, known as Haab striae, which can be seen when viewing the child’s red reflex. In extreme cases, when Descemet’s membrane tears, the cornea can become completely hydrated; this is called corneal hydrops.

Buphthalmos:

Increased intraocular pressure in glaucoma can also lead to buphthalmos (See
Figure 1), enlargement of the globe, and in turn cause a pseudoproptosis. A child’s eye is much more elastic than an adult eye, thus accounting for the increased corneal diameter and buphthalmos that we see in this disease. Descemet’s membrane and the corneal endothelium are less tolerant to high pressures and are therefore the tissues in which we see pathologic changes.

Conjunctival injection and strabismus:

Conjunctival injection and strabismus are less specific exam findings in infantile glaucoma.

Increased cup to disc ratio of the optic nerve:

The optic nerve exam in a patient with glaucoma typically reveals an increased cup to disc ratio with vertical elongation of the cup (See Figure 2), and asymmetry between the two eyes. This exam, often documented by serial photography, is the most useful tool we have in ophthalmology to determine the progression or stability of glaucoma, especially in the pediatric population. Interestingly in children, unlike adults, changes in the optic nerve head appearance can be reversed with treatment. Unfortunately, improvement in the appearance of the nerve does not necessarily predict improved function.

Figure 2.

Increased axial length in an infant’s eye can indicate glaucoma, and monitoring of axial length can be used to assess the stability of the disease. Axial length is determined with ultrasound on the anesthetized eye. A normal axial length in an infant is about 17 mm. Any eye with an axial length of 20 mm or more, asymmetry between the two eyes, or increasing myopia should prompt a thorough evaluation for glaucoma. The worsening myopia seen in pediatric glaucoma is due to this increased axial length and can be determined in a preverbal child by retinoscopy -- the use of a streak of light and the patient’s red reflex to determine refractive error.

Increased Intraocular Pressure:

Intraocular pressure is measured by the ophthalmologist using a hand held tonometer after topical anesthetic is applied to the cornea. This is sometimes performed under anesthesia, as it is difficult to get accurate readings in the awake child. Care should be taken to check IOP promptly after administration of anesthesia as anesthetic agents can alter IOP. A normal IOP for an infant is 10-15 mmHg. Pressures of 25 mmHg or higher are often present in children with primary infantile glaucoma.

Physical findings in secondary glaucoma

In secondary glaucoma, there are other characteristic physical exam findings that help lead the physician to diagnosis. When glaucoma is caused by Sturge-Weber, the characteristic port wine stain is seen on physical exam. The mechanism of glaucoma in these children is due to increased episcleral venous pressure, and not a maldeveloped angle. In patients with aniridia, an absent iris would be seen on physical exam and there is often family history of aniridia. Retinopathy of prematurity is often diagnosed in screening exams. Retinoblastoma most commonly presents with leukocoria, but can be subtle and only found on examination under anesthesia.

Other rare abnormalities of the anterior segment such as Peter’s Anomoly or Axenfeld-Reiger syndrome can also cause glaucoma.

What other disease/condition shares some of these symptoms?

Epiphora

Epiphora is very common in infancy, typically due to nasolacrimal duct obstruction. Since nasolacrimal duct obstruction is so prevalent, epiphora in a patient with primary infantile glaucoma is often dismissed until corneal clouding or other symptoms are recognized. Initially, corneal edema does not appear as a white cornea and can only be noticed when measured by a
pachymeter; however, it is sometimes noticeable if the two eyes appear to be different colors. Other causes of epiphora include corneal abrasion and conjunctivitis, which are acute and self-limited conditions.

Congenital Hereditary Endothelial Dystrophy

Congenital Hereditary Endothelial Dystrophy (CHED) is a rare disorder causing bilateral corneal edema in an infant. The more severe recessive form can present at birth and can be easily confused with glaucoma. The autosomal dominantly inherited form is less severe and presents around 2 years of age. There have been a few cases reported of CHED and primary infantile glaucoma, but generally these patients have normal IOP and a normal corneal diameter.

x-linked Megalocornea

Increased corneal diameter can also occur in x-linked megalocornea (See Figure 3), a rare condition in which the corneal diameter is 13mm or greater. Pseudobuphthalmos can occur in exophthalmos or craniosynastosis, but measurement of corneal diameter will help differentiate these causes.

Figure 3.

Megalocornea Photo courtesy of Robert W. Enzenauer, MD

Birth Trauma

Birth trauma, usually caused by forceps, can cause breaks in Descemet’s membrane leading to corneal clouding. The breaks in Descemets in birth trauma are usually vertically oriented (as opposed to the horizontally oriented Haab striae found in primary infantile glaucoma), and are often associated with soft tissue injury around the eye.

Metabolic disease

Metabolic disease such as mucoplyscaccharidoses (Hurler, Sheie, and Morquio syndromes) can also cause corneal clouding that can be confused with corneal edema.

Infection

Lastly, congenital infections such as rubella and syphilis can cause corneal clouding that can be confused with the corneal edema seen in primary infantile glaucoma.

What caused this disease to develop at this time?

In order to have high intraocular pressure, an eye must either have poor aqueous outflow or increased aqueous production. The latter is not considered to be an important factor in the pathogenesis of glaucoma. Aqueous drainage of an eye occurs mostly between the cornea and the iris in a location called the angle. After aqueous humor enters the angle, it drains through the trabecular meshwork, a fenestrated structure that empties into the canal of Schlemm and finally into the venous system. A smaller percentage (approximately 10%) of aqueous fluid exits the eye directly in a method termed uveoscleral outflow. Primary infantile and childhood glaucomas are caused by maldevelopment of the angle structures and poor aqueous outflow.

The degree to which the angle structures are abnormal determines the severity and the timing of the glaucoma; the earlier that the patient presents with symptoms, the more severe the disease. Only about 1 in 4 patients with primary infantile glaucoma will have signs at birth.

The increase in intraocular pressure (IOP) caused by poor aqueous outflow results in damage to the optic nerve head, peripheral vision loss, and ultimately central vision loss. The mechanism by which increased IOP causes vision loss is still debated; top theories support a mechanical loss of neurons and a vascular insult to nerve tissue.

What laboratory studies should you request to help confirm the diagnosis of glaucoma? How should you interpret the results?

There are no laboratory tests that will assist in making the diagnosis of primary infantile or juvenile glaucoma.

Would imaging studies be helpful? If so, which ones?

Imaging studies are not used to diagnose glaucoma.

If you are able to confirm that the patient has glaucoma, what treatment should be initiated?

Primary infantile glaucoma is almost always treated surgically. Ophthalmology consultation is indicated to confirm the diagnosis and begin treatment. The ophthalmologist will confirm bedside exam with measurement of corneal diameter and intraocular pressure and will also perform a slit lamp examination looking for corneal edema and Haab striae. Usually an examination under anesthesia will be performed to measure corneal thickness using pachymetry, axial length of the eye using ultrasound, intraocular pressure, and an examination of the optic nerve and the drainage system using ophthalmoscopy and gonioscopy respectively.

Occasionally medical therapy with topical IOP lowering drops is used as a temporizing measure before surgery. The drops used to lower IOP in children are B-blockers, carbonic anhydrase inhibitors, and prostaglandin analogs. Sometimes lowering IOP with these medications can make the cornea more clear and help facilitate goniotomy surgery. These drops are also used as an adjunct to surgery in some cases to further lower IOP.

Goniotomy and trabeculotomy are the two initial surgical procedures used to treat primary infantile glaucoma. The ophthalmologist will often perform goniotomy or trabeculotomy at the same time as the examination under anesthesia. In goniotomy, a goniotomy knife is used to cut the abnormal trabecular meshwork until Schlemm’s canal is reached. This is done under direct visualization using a gonioscopy lens and thus requires a clear cornea (See Figure 4).

Figure 4.

Goniotomy Photo courtesy of Robert W. Enzenauer, MD

Trabeculotomy is the alternative procedure and used when the cornea is not clear enough to perform goniotomy. In this surgery, a partial thickness scleral flap is created and an instrument called a trabeculotome is threaded into Schlemm’s canal. Then it is rotated to enter the anterior chamber, this tearing through the abnormal trabecular meshwork. Both of these procedures are first performed on 100-120 degrees of the trabecular meshwork and thus can be repeated at a later time on the unoperated portions of the eye. If these surgeries are not effective in lowering IOP, the next steps are for a filtering procedure such as a trabeculectomy or placement of a seton (a drainage device).

What are the possible outcomes of glaucoma?

While long term IOP control is often achieved in patients with pediatric glaucoma, these children still have decreased visual acuity and increased risk of strabismus and amblyopia compared to their unaffected counterparts. Primary infantile glaucoma causes 4-18% of childhood blindness. Approximately 30-40% of children with glaucoma will retain the vision to pass a driving license. Vision loss is common in pediatric glaucoma due to a combination of factors. There can be a loss of vision from the glaucoma itself or from deprivational or refractive amblyopia.

At present, lowering IOP is the only mechanism by which glaucoma can be treated. Decreasing IOP can slow the progression of glaucoma and advances in both the diagnosis and treatment of this disease have decreased the incidence of blindness in children due to glaucoma.

What causes this disease and how frequent is it?

Primary infantile glaucoma occurs in 1:10,000-1:15,000 live births in the United States. The highest reported rates in the world are in Saudi Arabia (1:2500) and the gypsy population in Romania (1:1,250) and the lowest are in Northern Ireland (1:22,000). The disease is bilateral in about 80% of cases. European and North American boys are more likely to have primary infantile glaucoma than their female counterparts, but the opposite sex preference has been reported in Japan.

It is much more common for a child to have a secondary glaucoma due to cataract extraction (with or without intraocular lens implantation) than to have primary infantile glaucoma. The role of intraocular lens implantation versus aphakia (absence of lens in the eye) with contact lens use on risk of glaucoma is currently being investigated. Aphakic glaucoma occurs in approximately 11-41% of aphakic children.

The etiology of primary infantile glaucoma is unknown. There is a possible link to mutations in the cytochrome P-450 gene. It is considered by most to be a sporadic disease with some reports suggesting autosomal recessive inheritance with variable penetrance.

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